Clinical Burden of Recurrent Disease in High-Risk Endometrial Cancer

Disease-free survival (DFS) is commonly a primary endpoint in clinical trials of investigational therapies for early stage and/or high-risk endometrial cancer and may be indicative of therapeutic benefit prior to maturity of overall survival (OS) data; however, its role as a predictor of OS in high-risk endometrial cancer is unknown. Therefore, this study estimates the individual-level correlation between DFS and OS and the association between recurrent disease and OS in patients with high-risk endometrial cancer receiving adjuvant chemotherapy.

Medicare beneficiaries with high-risk endometrial cancer who underwent surgery followed by adjuvant chemotherapy were identified from Surveillance, Epidemiology, and End Results data (2007-2019). OS and DFS from adjuvant chemotherapy initiation were estimated by Kaplan-Meier (KM) analyses; correlation was evaluated using Kendall's τ rank correlation. Multivariable Cox models were used to compare OS between recurrent and nonrecurrent patients at three landmark points and over the follow-up period.

Among 771 patients, 250 (32.4%) experienced recurrence (median follow-up 3.6 years). Median OS was not reached (5-year OS 72.7%); median DFS was 7.9 years (5-year DFS 58.1%). A positive correlation between DFS and OS was observed [Kendall's τ = 0.83; 95% confidence interval (CI) 0.79‒0.86; p < 0.001]. Across landmark points, recurrent patients had 3.8-5.2-fold higher risk of mortality (all p < 0.001). During follow-up, patients with recurrence had a higher risk of mortality than those without (hazard ratio 7.9; 95% CI 5.7‒10.8; p < 0.001).

The findings of this study suggest that DFS may be a useful surrogate for OS in high-risk endometrial cancer, though validation in trial-level meta-analyses is needed, and highlight the substantial burden associated with recurrent disease, as evidenced by the four-fold to eight-fold higher risk of mortality across comparative assessments of OS. Effective novel therapies are needed to reduce the considerable burden of disease recurrence in this population.